Last month, we explained the drug development process and pre-clinical studies. This month we’re going to answer a question a lot of biotech investors have — what are clinical drug trials and what are they for?

This article will describe the rigorous process of clinical trials in human subjects, which all medications must undergo before approval. Every drug lining your local pharmacy shelves has undergone clinical trials, over many years, before the U.S. Food & Drug Administration (FDA) gave its stamp of approval.

Only then can biotech companies market their drugs to consumers and collect revenue. Here’s how it works:

How Clinical Trials Begin

Clinical trials determine how drugs will interact with the human body, but first, the drug in question must have an approved marketing application to be transported across state lines. To get started, researchers must submit an Investigational New Drug (IND) application to the FDA, which includes the design of the clinical trials.

Clinical trials are designed by determining appropriate selection criteria for the human participants, the number of subjects who will participate, the duration of the trials, appropriate controls necessary to determine whether the effects observed is actually due to the drug, and the administration and dosage of the drug.

Additionally, it is key to perform appropriate assessments, data collection, review and analysis methods.

The IND review team at the FDA consists of several scientists contributing their particular expertise to evaluating the applications (pharmacologists, chemists, statisticians, medical officer, etc.). Applications are then either approved or placed on clinical hold if aspects of the application are deemed inadequate; however, this is rare.

While the FDA is available to provide feedback and assistance to the researchers, the researchers are given considerable freedom in performing the clinical research if their experimental design is sound.

Those that are recruited for clinical trials are typically a mix of healthy people who desire to further drug research and patients with the conditions purported to be treated by the drug. All drugs currently undergoing clinical trials can be found on clinicaltrials.gov.

The Phases of Clinical Trials

The process of approving a single new medication takes, on average, ten years and costs $2.6 billion. This multi-phase process is very time intensive and resource-heavy to ensure consumers access to safe and efficacious drugs.

Each of the three phases of clinical trials is considered a separate trial and requires data submission to the FDA before moving on to the next phase. Phase 0 trials can be performed on very small groups (fewer than 15 subjects) as an exploratory study to determine if small doses of the drug have any effect in humans; however, this is not required and is very rare.

1. Phase I clinical trials are performed to evaluate the safety of a drug, typically with a group of 20 to 100 volunteers. The researchers study how the lifecycle of the drug — from absorption to metabolization to excretion — along with identifying and recording side effects correlated with increased dosage. It’s a time-consuming process that can last several months. Further, there’s no guarantee that a drug will make it through the first phase, as only about 70% of drugs pass this phase.
2. Phase II clinical trials determine the efficacy of the drug, with several hundred patients. Subjects are randomly sorted into either the experimental or control group, with the controls receiving a placebo instead of the drug. The trials are typically double-blind, with neither patients nor researchers knowing what the subjects are receiving. This is done to remove bias. This phase can last anywhere from a couple of months to a couple of years. After all that time, only about 33% of drugs moving on to phase III.
3. Phase III clinical trials further evaluate the efficacy of the drug, along with its long-term effects. Between 300 and 3,000 patients are recruited for the trial and monitored from 1 to 4 years. About 25% to 30% of drugs pass this phase.

Clinical Trial Outcomes

Often, issues will arise during clinical trials ensuring certain drugs never become approved for the market unless they’re resolved through further studies and tests.

If the drug passes the phase III clinical trials, the researchers file a New Drug Application (NDA) with the FDA, which must include all data showing the safety and effectiveness of the drug.

If the FDA determines that the human clinical trials for the drug have proven the treatment as safe for mass consumption in humans, then it’s one step closer to lining your pharmacy shelves.